title: Effects of specific multi-nutrient enriched diets on cerebral metabolism, cognition and neuropathology in AβPPswe-PS1dE9 mice.
abstract: Recent studies have focused on the use of multi-nutrient dietary interventions in search of alternatives for the treatment and prevention of Alzheimer's disease (AD). In this study we investigated to which extent long-term consumption of two specific multi-nutrient diets can modulate AD-related etiopathogenic mechanisms and behavior in 11-12-month-old AβPPswe-PS1dE9 mice. Starting from 2 months of age, male AβPP-PS1 mice and wild-type littermates were fed either a control diet, the DHA+EPA+UMP (DEU) diet enriched with uridine monophosphate (UMP) and the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), or the Fortasyn® Connect (FC) diet enriched with the DEU diet plus phospholipids, choline, folic acid, vitamins and antioxidants. We performed behavioral testing, proton magnetic resonance spectroscopy, immunohistochemistry, biochemical analyses and quantitative real-time PCR to gain a better understanding of the potential mechanisms by which these multi-nutrient diets exert protective properties against AD. Our results show that both diets were equally effective in changing brain fatty acid and cholesterol profiles. However, the diets differentially affected AD-related pathologies and behavioral measures, suggesting that the effectiveness of specific nutrients may depend on the dietary context in which they are provided. The FC diet was more effective than the DEU diet in counteracting neurodegenerative aspects of AD and enhancing processes involved in neuronal maintenance and repair. Both diets elevated interleukin-1β mRNA levels in AβPP-PS1 and wild-type mice. The FC diet additionally restored neurogenesis in AβPP-PS1 mice, decreased hippocampal levels of unbound choline-containing compounds in wild-type and AβPP-PS1 animals, suggesting diminished membrane turnover, and decreased anxiety-related behavior in the open field behavior. In conclusion, the current data indicate that specific multi-nutrient diets can influence AD-related etiopathogenic processes. Intervention with the FC diet might be of interest for several other neurodegenerative and neurological disorders.
authors.affiliation: Department of Anatomy, Radboud University Nijmegen Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors.forename: Diane
authors.initials: D
authors.lastname: Jansen
authors.forename: Valerio
authors.initials: V
authors.lastname: Zerbi
authors.forename: Ilse A C
authors.initials: IA
authors.lastname: Arnoldussen
authors.forename: Maximilian
authors.initials: M
authors.lastname: Wiesmann
authors.forename: Anne
authors.initials: A
authors.lastname: Rijpma
authors.forename: Xiaotian T
authors.initials: XT
authors.lastname: Fang
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Dederen
authors.forename: Martina P C
authors.initials: MP
authors.lastname: Mutsaers
authors.forename: Laus M
authors.initials: LM
authors.lastname: Broersen
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Miller
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: Arend
authors.initials: A
authors.lastname: Heerschap
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Kiliaan
mesh_terms: D000544:Alzheimer Disease / Q000178:diet therapy* / Q000517:prevention & control*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D005227:Fatty Acids / Q000378:metabolism; D005527:Food, Fortified / Q000032:analysis*; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008817:Mice, Mutant Strains; D060888:Real-Time Polymerase Chain Reaction; D014542:Uridine Monophosphate
chemical_list: D017931:DNA Primers; D005227:Fatty Acids; D053583:Interleukin-1beta; D004281:Docosahexaenoic Acids; D002784:Cholesterol; D015118:Eicosapentaenoic Acid; D014542:Uridine Monophosphate